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Ultrasound Contrast Agents Loaded with Magnetic Nanoparticles: Acoustic and Mechanical Characterization
KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
2013 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

The current methodologies in body scanning diagnostic uses different simultaneous imaging modalities like Ultrasound (US), magnetic resonance imaging (MRI), single photon emission tomography (SPECT) and positron emission tomography (PET). The field requires combination of different modalities for effective use in clinical diagnostics. Such incorporation of different modalities has already been achieved. For example, PET-CT hybrid scanner is designed to acquire align functional and anatomical images and recently US-MRI scanner has successfully shown to improve diagnosis of prostate cancer. The non ionizing radiation hybrid US-MRI is of great interest in health care industry. Further these US and MRI modalities uses different contrast agents like micro-sized gas bubbles (MBs) encapsulated by surfactant for US and superparamagnetic nanoparticles for MRI imaging modalities to further enables new diagnostic opportunities and therapeutic applications. Recently in our 3MiCRON project, we have developed the multimodal contrast agent that could be supported for both US and MRI. This was achieved by coating the magnetic nanoparticles to the poly vinyl alcohol (PVA) surfactant shelled MBs. The nanoparticles in the shell effect the structure can alter the MBs performance as an ultrasound contrast agent. The present thesis is conducted to examine the acoustic and mechanical properties of such multimodal contrast agents.

These multimodal contrast agents were prepared by coating the surface of PVA-shelled MBs by two following strategies: (1) The superparamagnetic iron oxide (Fe3O4) nano-particles (SPIONs) were chemically anchored to the surface of poly vinyl alcohol (PVA) shelled MBs namely MBs-chem and (2) in the second strategy the SPIONs were physical entrapped into the PVA shell while formation of PVA surface on the gas bubble were named as MBs-phys. To understand the scattering efficiency and viscoelastic properties of these modified agents, we investigated the backscattering power, attenuation coefficient and phase velocity measurements. Our acoustic experimental results indicate that both the modified MBs and non-modified plain PVA-shelled ultrasound contrast agents have the same echogenic response. The investigation of mechanical properties of modified MBs revealed that the attached SPIONs on the PVA shell has reduced the stiffness of MBs-chem shell, while, the SPIONs inside the shell has increased MBs-phys stiffness. As a result, MBs-chem exhibits soft shell behavior under ultrasound exposure than both MBs-phys. Finally, the images were obtained through the MRI investigations at the department of Radiology, Karolinksa Institute, has demonstrated that both MB types have enough magnetic susceptibility that further provides good detectability in vitro and in vivo. As an outlook, the modified magnetic gas bubbles, i.e. both MBs-chem and MBs-phys can be proposed as a potential contrast agent for both US and MR imaging and can be further utilized in potential therapeutic applications.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2013. , viii, 40 p.
Series
Trita-STH : report, ISSN 1653-3836 ; 2013:6
Keyword [en]
Ultrasound contrast agents, SPION nanoparticles, harmonic oscillation, backscattering power, attenuation coefficient, phase velocity, nonlinear equation of motion
National Category
Medical Engineering
Identifiers
URN: urn:nbn:se:kth:diva-134616ISBN: 978-91-7501-951-2 (print)OAI: oai:DiVA.org:kth-134616DiVA: diva2:667221
Presentation
2013-12-06, Room 7B, Alfred Nobels Allé 8 Flemingsberg, Stockholm, 13:00 (English)
Opponent
Supervisors
Note

QC 20131126

Available from: 2013-11-26 Created: 2013-11-26 Last updated: 2013-11-26Bibliographically approved
List of papers
1. Magnetite Nanoparticles Can Be Coupled to Microbubbles to Support Multimodal Imaging
Open this publication in new window or tab >>Magnetite Nanoparticles Can Be Coupled to Microbubbles to Support Multimodal Imaging
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2012 (English)In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 13, no 5, 1390-1399 p.Article in journal (Refereed) Published
Abstract [en]

Microbubbles (MBs) are commonly used as injectable ultrasound contrast agent (UCA) in modern ultrasonography. Polymer-shelled UCAs present additional potentialities with respect to marketed lipid-shelled UCAs. They are more robust; that is, they have longer shelf and circulation life, and surface modifications are quite easily accomplished to obtain enhanced targeting and local drug delivery. The next generation of UCAs will be required to support not only ultrasound-based imaging methods but also other complementary diagnostic approaches such as magnetic resonance imaging or computer tomography. This work addresses the features of MBs that could function as contrast agents for both ultrasound and magnetic resonance imaging. The results indicate that the introduction of iron oxide nanoparticles (SPIONs) in the poly(vinyl alcohol) shell or on the external surface of the MBs does not greatly decrease the echogenicity of the host MBs compared with the unmodified one. The presence of SPIONs provides enough magnetic susceptibility to the MBs to accomplish good detectability both in vitro and in vivo. The distribution of SPIONs on the shell and their aggregation state seem to be key factors for the optimization of the transverse relaxation rate.

Keyword
Ultrasound Contrast Agents, Iron-Oxide Nanoparticles, Active Polymeric Microbubbles, Coated Microbubbles, Acoustic Properties, Induced Fracture, In-Vitro, Part I, Delivery, Shell
National Category
Medical Engineering
Identifiers
urn:nbn:se:kth:diva-96726 (URN)10.1021/bm300099f (DOI)000303951600019 ()2-s2.0-84861134310 (Scopus ID)
Note

QC 20150626

Available from: 2012-06-12 Created: 2012-06-11 Last updated: 2017-12-07Bibliographically approved
2. On the interplay of shell structure with low- and high-frequency mechanics of multifunctional magnetic microbubbles
Open this publication in new window or tab >>On the interplay of shell structure with low- and high-frequency mechanics of multifunctional magnetic microbubbles
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2014 (English)In: Soft Matter, ISSN 1744-683X, E-ISSN 1744-6848, Vol. 10, no 1, 214-226 p.Article in journal (Refereed) Published
Abstract [en]

Polymer-shelled magnetic microbubbles have great potential as hybrid contrast agents for ultrasound and magnetic resonance imaging. In this work, we studied US/MRI contrast agents based on air-filled poly(vinyl alcohol)-shelled microbubbles combined with superparamagnetic iron oxide nanoparticles (SPIONs). The SPIONs are integrated either physically or chemically into the polymeric shell of the microbubbles (MBs). As a result, two different designs of a hybrid contrast agent are obtained. With the physical approach, SPIONs are embedded inside the polymeric shell and with the chemical approach SPIONs are covalently linked to the shell surface. The structural design of hybrid probes is important, because it strongly determines the contrast agent's response in the considered imaging methods. In particular, we were interested how structural differences affect the shell's mechanical properties, which play a key role for the MBs' US imaging performance. Therefore, we thoroughly characterized the MBs' geometric features and investigated low-frequency mechanics by using atomic force microscopy (AFM) and high-frequency mechanics by using acoustic tests. Thus, we were able to quantify the impact of the used SPIONs integration method on the shell's elastic modulus, shear modulus and shear viscosity. In summary, the suggested approach contributes to an improved understanding of structure-property relations in US-active hybrid contrast agents and thus provides the basis for their sustainable development and optimization.

Keyword
Geometric feature, High frequency HF, Imaging performance, Integration method, Physical approaches, Structural differences, Structure property relation, Superparamagnetic iron oxide nanoparticles
National Category
Medical Engineering
Identifiers
urn:nbn:se:kth:diva-134611 (URN)10.1039/c3sm51560e (DOI)000327849000024 ()2-s2.0-84889577207 (Scopus ID)
Funder
EU, FP7, Seventh Framework Programme, 245572
Note

QC 20150626

Available from: 2013-11-25 Created: 2013-11-25 Last updated: 2017-12-06Bibliographically approved
3. Assessment of the viscoelastic and oscillation properties of a nanoengineered-shelled multimodality contrast agent
Open this publication in new window or tab >>Assessment of the viscoelastic and oscillation properties of a nanoengineered-shelled multimodality contrast agent
Show others...
(English)Manuscript (preprint) (Other academic)
Identifiers
urn:nbn:se:kth:diva-134612 (URN)
Note

QS 2013

Available from: 2013-11-25 Created: 2013-11-25 Last updated: 2013-11-26Bibliographically approved

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